Microbiota-mitochondria axis in neurodegenerative disorders and retinal dysfunction: mechanisms and emerging therapeutic opportunities

Abstract

The gut microbiota crucial role in maintaining host metabolism, immune homeostasis, intestinal integrity, and mitochondrial function. Emerging evidence suggests that dysregulation of the microbiota–mitochondria axis represents one of the key mechanisms linking gut dysbiosis to the development of neurodegenerative and ocular diseases. The dysbiosis causes disruptions in mitochondrial physiology due to lower levels of short-chain fatty acids, increased intestinal permeability, endotoxemia, oxidative stress, and inflammation. These mechanisms contribute to the pathogenesis of Alzheimer’s disease, Parkinson’s disease, age-related macular degeneration, diabetic retinopathy, retinitis pigmentosa, and central serous chorioretinopathy. Environmental factors such as unhealthy dietary patterns, excessive antibiotic use, and prolonged exposure to artificial blue light may exacerbate dysbiosis and further disrupt mitochondrial homeostasis, thereby contributing to disease progression. We also elaborated the emerging therapeutic strategies targeting both the gut microbiota and mitochondrial function, including next-generation probiotics, postbiotics, dietary interventions, mitochondria-targeted antioxidants, NAD+ precursors, and precision medicine approaches. Collectively, current evidence represents the microbiota–mitochondria axis as a one of the promising mechanistic and therapeutic targets for neurodegenerative and ocular diseases. However, most therapeutic evidence discussed in this review is derived from preclinical studies, with relatively limited clinical validation. Future well-designed longitudinal studies and randomized clinical trials are essential to establish efficacy, safety, and translational applicability in humans.